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Biomimetic Tools In Oxidative Metabolism: Characterization Of Reactive Metabolites From Antithyroid Drugs, Kudzanai Chipiso
Biomimetic Tools In Oxidative Metabolism: Characterization Of Reactive Metabolites From Antithyroid Drugs, Kudzanai Chipiso
Dissertations and Theses
Toxicities of sulfur-based drugs have been attributed to formation of highly reactive sulfur oxo-acids and depletion of glutathione by the formation of reactive metabolites. Metabolic activation of these sulfur centers to conceivably toxic reactive metabolites (RMs) that can covalently modify proteins is considered the initial step in drug-induced toxicity. Despite considerable effort and research, detection and characterization of these RMs during drug development and therapy remains a challenge. Methimazole (MMI) and 6-propyl-2-thiouracil (PTU) are two commonly used antithyroid, sulfur-based drugs. Though effective, these drugs are associated with idiosyncratic toxicity. PTU has acquired a black box warning and physicians are calling …